Despite basic and clinical research directed at understanding and controlling breast cancer, breast cancer is still a major health threat worldwide. Basal-like breast tumors (BL-BTs) or triple-negative breast cancers (TNBCs) are an especially aggressive group of tumors often found in young Afro-American and Hispanic women, with the shortest survival of all breast cancer subtypes, including luminal A, luminal B, HER2, normal-like, and claudin-low tumors. These tumors comprise ˜15% of human breast cancers, and more than 75% of breast cancers arising in women carrying a BRCA1 mutation.
TNBCs are estrogen receptor, progesterone receptor and HER2 negative (triple-negative), and can express different combinations of CK5, CK14, CK17, CK18 and/or EGFR. These tumors retain a mixed luminal/myoepithelial (i.e., progenitor-like) phenotype, and recent studies indicate that TNBCs derive from transformed mammary epithelial progenitors. Concomitant genetic ablation of RB and TP53, or BRCA1 alone, in the progenitor cell compartment of the mouse mammary gland induces the development of basal-like malignant tumors. Notably, mutations in TP53 and/or RB genes occur in over 90% of human BL-BTs.
BL-BTs have distinct morphological and cytological features. They are typically poorly differentiated lesions with high mitotic counts, central areas of necrosis, pushing borders and prominent stromal lymphocytic infiltrates. Basal-like cancer cells, which can be arranged in solid sheets or nests, are atypical and pleomorphic, and are highly enriched for cells with the CD44+/CD24low/− phenotype, which has been associated with tumor-initiating potential.
Despite response to front-line chemotherapy, tumors such as BL-BTs have a grim prognosis because of early relapse within the first five years of diagnosis. BL-BTs rapidly acquire resistance to chemotherapy and are refractory to endocrine therapy and HER-2 inhibitors. Therefore there is a need for identifying methods to diagnose and treat refractory tumors, such as basal-like breast tumors.